Quinuclidine derivative

Abstract

Provided are a quinuclidine derivative of formula (1) and a medicament comprising the quinuclidine derivative: wherein R 1 represents a hydrogen atom, a halogen atom, a lower alkyl group, a haloalkyl group, a lower alkoxy group, or a haloalkoxy group; Y represents —C(C═O)—O—, or —CH 2 O—; m represents an integer of 1 to 5; Z represents an oxygen atom or a sulfur atom; l represents a number of 0 or 1; n represents an integer of 0 to 4; X − represents an anion; and a substituent of a quinuclidine ring represents a 1,3-bond, or 1,4-bond, provided that when m is 3, l is 1, and n is 0, R 1 represents a halogen atom, a lower alkyl group, a haloalkyl group, a lower alkoxy group, or a haloalkoxy group.

The invention claimed is: 
     
       1. A quinuclidine derivative of the general formula (1): 
       
         
           
           
               
               
           
         
         wherein: 
         R 1  represents a hydrogen atom, a halogen atom, a lower alkyl group, a haloalkyl group, a lower alkoxy group, or a haloalkoxy group; 
         Y is —C(═O)—O; 
         m is an integer of 1 to 5; 
         Z is an oxygen atom or a sulfur atom; 
         l is 0; 
         n is an integer of 0 to 4; and 
         X −  is an anion; 
         substituents of a quinuclidine ring in the formula (1)are in a 1,3-position or 1,4-position. 
       
     
     
       2. The quinuclidine derivative according to  claim 1 , wherein:
 m is an integer of 2 to 5; and 
 n is a number of 0 or 1. 
 
     
     
       3. The quinuclidine derivative according to  claim 1 , wherein n is 0. 
     
     
       4. The quinuclidine derivative according to  claim 1 , wherein
 m is 3. 
 
     
     
       5. The quinuclidine derivative according to  claim 1 , wherein the quinuclidine derivative is an (R) isomer. 
     
     
       6. A pharmaceutical composition, comprising the quinuclidine derivative of  claim 1 , and a pharmaceutically acceptable carrier. 
     
     
       7. A method for treating chronic obstructive pulmonary disease, the method comprising administering an effective amount of the quinuclidine derivative according to  claim 1 . 
     
     
       8. The pharmaceutical composition of  claim 6 , wherein the pharmaceutical composition is in the form of an inhalant, a transairway agent, a nose drop, an injection, a tablet, a granule, a powder, a capsule, an ointment, a cream, a patch, a suppository, or a combination thereof. 
     
     
       9. The pharmaceutical composition of  claim 6 , wherein the quinuclidine derivative is included in an amount of at least 0.01% by mass based on the total amount of the composition. 
     
     
       10. The pharmaceutical composition of  claim 6 , wherein the quinuclidine derivative is included in an amount of at least 1% by mass based on the total amount of the composition. 
     
     
       11. The method of  claim 7 , wherein 1.0 μg to 10 mg of the quinuclidine derivative is administered per day. 
     
     
       12. The method of  claim 7 , wherein the quinuclidine derivative is administered via transnasal or transpulmonary administration. 
     
     
       13. The quinuclidine derivative of  claim 1 , wherein:
 m is 3; and 
 n is 0. 
 
     
     
       14. A pharmaceutical composition, comprising the quinuclidine derivative of  claim 2 , and a pharmaceutically acceptable carrier. 
     
     
       15. A method for treating chronic obstructive pulmonary disease, the method comprising administering an effective amount of the quinuclidine derivative of  claim 2 . 
     
     
       16. The pharmaceutical composition of  claim 14 , wherein the pharmaceutical composition is in the form of an inhalant, a transairway agent, a nose drop, an injection, a tablet, a granule, a powder, a capsule, an ointment, a cream, a patch, a suppository, or a combination thereof. 
     
     
       17. A pharmaceutical composition, comprising the quinuclidine derivative of  claim 3 , and a pharmaceutically acceptable carrier. 
     
     
       18. A method for treating chronic obstructive pulmonary disease, the method comprising administering an effective amount of the quinuclidine derivative of  claim 3 . 
     
     
       19. The pharmaceutical composition of  claim 17 , wherein the pharmaceutical composition is in the form of an inhalant, a transairway agent, a nose drop, an injection, a tablet, a granule, a powder, a capsule, an ointment, a cream, a patch, a suppository, or a combination thereof.